Gene mapping study shows promise, challenges

Friday, March 14, 2014

CHICAGO (AP) — These days, it's faster and cheaper than ever to decipher a person's entire DNA. But a small study suggests that looking for disease risks that way may not be ready for the masses.

For one thing, the research found that gene variants most likely linked with significant disease were the least likely to be accurately identified.

And analyzing the mass of data from the DNA scan is a daunting task, researchers said.

Some experts think more targeted gene-mapping is a better approach. But while whole genome sequencing is mostly done for research, it has far-reaching potential for diagnosing and treating genetic diseases, even in people with no known risks. The new results show its promise and its challenges.

Stanford University researchers performed whole genome sequencing in 12 healthy people. Most of the millions of genetic variants they found were of uncertain significance, although one woman was found to have a high genetic risk for cancer.

DNA is recovered by a simple blood test and deciphered by machines. The difficulty lies in interpreting the findings and figuring out which variants are important and which ones can be ignored. That takes days of sophisticated follow-up lab tests and interpretation to reveal potentially meaningful genetic information, the researchers said.

Dr. Euan Ashley, a senior co-author and Stanford associate professor of medicine and genetics, likened the technology to "an unruly teenager who has grown up very fast. There's huge potential."

"This paper is like parental tough love — we have to be really honest about where we are in order to bring it up to clinical standards," he said.

For the test, they used two commercially available instruments to sequence the DNA — the second one to validate the initial findings. But less than one-third of variants in inherited disease genes were confirmed.

Several specialists including medical geneticists, genetic counselors and a pathologist examined the findings and recommended follow-up tests. Medical intervention was considered appropriate for one participant, a woman with no family history of breast or ovarian cancer found to have a genetic variant strongly linked with those diseases. That finding led to surgery to remove her ovaries and increased breast cancer screening.

The cost per patient was about $17,000 plus hundreds of dollars in follow-up tests. Some centers charge less and the cost is expected to drop considerably as the technique is improved.

The study was published Tuesday in the Journal of the American Medical Association. Ashley and several co-authors have financial ties to a genome interpretation company and receive royalties for patents related to genome sequencing. One of the authors has received speaker fees from the maker of one of the machines used.

The research and previous studies "provide a glimpse of what is possible" for technology that eventually will be widely used for patients, a JAMA editorial said.

"Like the personal computer, Internet, smartphones, and electronic health records, turning back now from the use of genomic technologies in health care is inconceivable," wrote contributing JAMA editor Dr. William Gregory Feero, former special adviser to the director of the National Human Genome Research Institute.